The proposed research covers four major areas which are closely inter-related. They are: 1) Characterization and isolation of the growth factors present in the special conditioned medium. One or more of these factors will permit cloning of leukemic cells from patients with a high cloning efficiency (60-100%). This system has the potential to provide optimal material for a variety of biochemical and immunological studies relevant to the management of leukemic patients. 2) Drug development studies for anti-tumor agents in culture and in animal. The new compounds will be evaluated in a cell culture system and preliminary work concerning molecular sites of action investigated. The active new compounds will then be evaluated in murine transplantable tumor systems with survival, pharmacology and toxicology studies. 3) Drug combination studies and acute cell death of leukemic cells in culture and in animal have been continued, with emphasis on the mode of action of synergistic effect of methotrexate on cytosine arabinoside and on selenoguanosine.